The primary objective is to determine the pathogenesis of the disorder amyloidosis by a study of data relating to its biochemistry, immunology, pathogenesis and interaction of the various components which are presently known to be present in amyloid-rich tissues. The components include the immunoglobulin related type amyloid fibril found to be the main constituent in primary amyloids, the smaller molecular weight protein A found to be predominant in secondary and hereditary amyloids and the P-component known to be present in all amyloids and antigenically identical to a component in normal serum. Plans in the area of immunochemistry include further characterization of the A protein from the casein model of mouse amyloid. Further studies to outline the mechanisms involved in antibody formation suppression by protein SAA are planned. Isolation of amyloid-P-component from serum by affinity chromatography will be continued so that studies of primary structure can be made and compared to sequence studies already accomplished on tissue derived P-component. We also plan additional comparative chemical characterization and sequences on newly isolated and purified amyloid fibrils and complete sequence analyses of the AA protein and sequence analysis of the serum AA protein when isolated. In addition, fine structural studies are planned in the relationship of amyloid deposits to structural elements of striated muscle at an ultrastructural level. We shall further explore the role of colchicine and other substances as prophylactic and therapeutic agents in experimental amyloidosis. Finally, electron microscopic investigations on synovial cells from experimental, immunized and normal rabbits will be pursued. BIBLIOGRAPHIC REFERENCES: Benson, M.D., Skinner, M. and Cohen, A.S.: Antigenicity and cross-reactivity of denatured fibril proteins of primary, secondary and myeloma-associated amyloids. J. Lab. and Clin. Med. 85:650, 1975. Benson, M.D., Cohen, A.S., Brandt, K.D. and Cathcart, E.S.: Neuropathy, M-components and amyloid. Lancet 1:10, 1975.